Broad baseline-variable profiling of visceral conversion in bone-only HR+/HER2 − metastatic breast cancer treated with CDK4/6 inhibitors

BACKGROUND: Bone-only HR+/HER2 - metastatic breast cancer generally has a favourable prognosis, but some patients develop visceral metastases. We aimed to quantify visceral conversion and identify reproducible baseline correlates during CDK4/6 inhibitor (CDK4/6i) therapy. METHODS: This multicentre retrospective cohort included 692 patients treated with palbociclib, ribociclib, or abemaciclib plus endocrine therapy as first- or second-line treatment across 24 Italian centres. Visceral conversion was analysed in a competing-risks framework, with skeletal progression or death without prior visceral conversion as competing events. Eighteen baseline candidate predictors derived from a 35-variable dataset were evaluated using Fine-Gray modelling, ridge penalisation, bootstrap stability assessment, and cause-specific Cox sensitivity analyses. RESULTS: Over a median follow-up of 31 months, 162 patients (23.4%) developed visceral conversion after a median of 17.0 months. Cumulative incidence was 8.8%, 17.5%, and 24.5% at 12, 24, and 36 months, respectively; median overall survival after visceral conversion was 18.0 months. Progesterone receptor (PR) expression was the most stable tumour-biological correlate, with complete sign concordance and a median absolute coefficient rank of 1 across 500 bootstrap resamples. In the mutually adjusted Fine-Gray model, higher PR expression was associated with lower visceral-conversion risk (sHR per 10-percentage-point increase, 0.929; 95% CI, 0.889-0.971; p = 0.0012), with consistent direction across complementary analyses. However, stand-alone PR prediction remained modest (24-month IPCW AUC, 0.585; Brier score, 0.142; IPA, 1.1%; O:E, 1.00), limiting individual-level clinical utility. CONCLUSIONS: Broad baseline-variable profiling identified PR expression as the most reproducible tumour-biological correlate of visceral conversion, although its stand-alone predictive performance was modest.